Reviews & Analysis

Rheumatoid arthritis synovium contains phenotypically and functionally heterogeneous fibroblast-like synoviocytes. Cutting-edge analyses have now defined at least four distinct states of these cells related to their location in the synovium, epigenetic imprinting and the influence of microenvironment mediators.

The rise in the use of digital health-care technologies such as electronic patient-reported outcome measures enables a transformation of the traditional care model. In light of the increasing demand for rheumatologists, telehealth could enable more efficient usage of scarce face-to-face appointments.

The TNF–TNF receptor signalling network has pleiotropic effects that can both promote and protect against immune-mediated diseases. Modulation of this network through the use of TNF receptor-targeting biologic drugs holds promise for treating various diseases, including TNF inhibitor-refractory diseases.

Drug-free remission is a treatment goal in rheumatoid arthritis that can be achieved by tapering and discontinuation of biologic DMARDs. However, newly published real-world evidence suggests that DMARD discontinuation occurs less frequently than results of clinical trials suggest, so it is important to question what the ultimate goal of treatment should be.

The pathogenesis of juvenile dermatomyositis (JDM) is complex and various evidence implicate a role for type I interferons. Could the use of a bioengineered paediatric skeletal muscle model provide insight into this disease and have potential for high throughput testing of therapeutic agents?

In this Review the authors outline the evidence for how sleep disturbance and inflammation interact in a positive feedback spiral in rheumatoid arthritis, leading to further inflammation, pain and progression of disease activity.

The rarity of various forms of vasculitis, as well as other rheumatic diseases, presents difficulties in studying the genetics of these diseases as well as for evaluating treatments. Might new approaches, such as joint genetic analyses and drug repurposing, provide opportunities to learn more about these diseases and identify new therapies and serve as a basis for basket clinical trials?

Vaccines are important tools for protection against infectious diseases, particularly in patients undergoing immunosuppression (including DMARD therapy). This Review discusses the effects of DMARDs on vaccine immunogenicity, focusing on influenza and SARS-CoV-2 vaccines, and potential mechanisms underlying these effects.

In this Consensus Statement, the Treatment Response Measure for Systemic Lupus Erythematosus Consortium presents the initial outcomes of a project to develop a clinical outcome assessment that can contribute to the regulatory approval process for therapeutic agents via its incorporation in end points of clinical trials in systemic lupus erythematosus.

In this Perspective, the authors discuss molecular, cellular and imaging evidence in spondyloarthritis that supports a bone marrow rather than an entheseal origin. Focusing on immune cells and dysfunction in the bone marrow niche could redirect the therapeutic approach to spondyloarthritis.

The potential for the co-occurrence of spondyloarthritis and inflammatory bowel disease means that gastroenterologists must identify articular manifestations and rheumatologists must identify intestinal manifestations. This Review describes the progress in the treatment of patients with both spondyloarthritis and inflammatory bowel disease.

This Review provides an overview of the complement system and its role in a range of rheumatic and autoimmune diseases, and examines the rapidly expanding landscape of complement therapeutics in these settings, as well as prospects for improving their clinical use.

No drugs are yet approved for the treatment of primary Sjögren syndrome, despite a large number of clinical trials. Non-conventional approaches can help to identify novel therapeutic targets. Using a drug-repositioning transcriptomic approach, interferon has emerged once again as a major target for intervention in this disease process.

Post-transcriptional regulation of gene expression is important in various cellular processes, and disruption of this process can lead to aberrant immune responses, including autoimmune processes. This Review discusses the role of post-transcriptional checkpoints in autoimmunity and potential therapeutic implications.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are increasingly viewed as parts of a single disease spectrum. In this Review, the authors outline how stratification of patients with GCA–PMR spectrum disease using clinical, imaging and laboratory data can to help guide therapy.

Cartilage defects often fail to heal, which can lead to degenerative changes and ultimately to osteoarthritis. This Review discusses various hypotheses for why articular cartilage fails to regenerate and accompanying potential therapeutic solutions.

Rheumatoid arthritis is associated with an excess risk of atherosclerotic cardiovascular disease. This Review summarizes shared inflammatory pathways between rheumatoid arthritis and atherosclerotic cardiovascular disease that are targeted by existing therapies, and lessons learnt from clinical trials of these drugs.

Bone marrow lesions (BMLs) are considered possible biomarkers and therapeutic targets in osteoarthritis, but human studies of BMLs have important limitations. In this Review, the authors explore the utility and potential of animal models in BML research.

This Review provides an overview of the clinical features and subtypes, pathophysiology and management of juvenile idiopathic inflammatory myopathies, including updates to our understanding of this heterogenous group of diseases that might change clinical practice in the near future.

Matrix metalloproteinases contribute to irreversible joint remodelling in the pathogenesis of joint diseases, including rheumatoid arthritis and osteoarthritis. This article reviews several aspects of matrix metalloproteinase biology related to arthritis and discusses how they relate to opportunities for precision medicine and diagnosis.